Characterization of the transcription factor Gfi1 as novel regulator of bone homeostasis

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The transcription factor growth factor independent 1 (GFI1) is a negative regulator of hematopoietic stem cell (HSC) proliferation. Loss of Gfi1 induces neutropenia, lymphocyte deficiency, and monocyte accumulation. It is well established that the HSC pool is regulated by osteoblasts; however, whether HSC regulate osteoblasts or MSC differentiation is poorly characterized. We demonstrate that Gfi1 knock-out mice (Gfi1-/-) show a progressive bone loss (osteoporosis), which is in line with the osteoporotic phenotype in patients suffering from chronic idiopathic neutropenia. This project aims to define the underlying mechanism of osteoporosis in Gfi1-/- mice. Moreover, we intend to characterize the influence of a presumably altered HSC pool on osteoblasts within the stem cell niche in Gfi1-/- mice.